Considerations for understanding protein measurements: Identification of formation, degradation and more pathological relevant epitopes.

OBJECTIVES: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selected biomarkers. In population-based research, variation may be somewhat eliminated by quantity. However, this fascination of numbers may limit the attention to and understanding of the single. This review highlights that protein measurements (with collagens as examples) may mean different things depending on the targeted epitope - formation or degradation of tissues, and even signaling potential of proteins. DESIGN AND METHODS: PubMed was searched for collagen, neo-epitope, biomarkers. RESULTS: Ample examples of assays with specific epitopes, either pathological such as HbA1c, or domain specific such as pro-peptides, which total protein arrays would not have identified were evident. CONCLUSIONS: We suggest that big data may be considered as the funnel of data points, in which most important parameters will be selected. If the technical precision is low or the biological accuracy is limited, and we include suboptimal quality of biomarkers, disguised as big data, we may not be able to fulfill the promise of helping patients searching for the optimal treatment. Alternatively, if the technical precision of the total protein quantification is high, but we miss the functional domains with the most considerable biological meaning, we miss the most important and valuable information of a given protein. This review highlights that measurements of the same protein in different ways may provide completely different meanings. We need to understand the pathological importance of each epitope quantified to maximize protein measurements.

Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. METHODS: Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. RESULTS: Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. CONCLUSION: Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

Centralization of Pancreatic Surgery Improves Results: Review.

BACKGROUND AND AIMS: The effect of operation volume on the outcomes of pancreatic surgery has been a subject of research since the 1990s. In several countries around the world, this has led to the centralization of pancreatic surgery. However, controversy persists as to the benefits of centralization and what the optimal operation volume for pancreatic surgery actually is. This review summarizes the data on the effect of centralization on mortality, complications, hospital facilities used, and costs regarding pancreatic surgery. MATERIALS AND METHODS: A systematic librarian-assisted search was performed in PubMed covering the years from August 1999 to August 2019. All studies comparing results of open pancreatic resections from high- and low-volume centers were included. In total 44, published articles were analyzed. RESULTS: Studies used a variety of different criteria for high-volume and low-volume centers, which hampers the evaluating of the effect of operation volume. However, mortality in high-volume centers is consistently reported to be lower than in low-volume centers. In addition, failure to rescue critically ill patients is more common in low-volume centers. Cost-effectiveness has also been evaluated in the literature. Length of hospital stay in particular has been reported to be shorter in high-volume centers than in low-volume centers. CONCLUSION: The effect of centralization on the outcomes of pancreatic surgery has been under active research and the beneficial effect of it is associated especially with better short-term prognosis after surgery.

Pancreatic resections are not only safest but also most cost-effective when performed in a high-volume centre: A Finnish register study.

BACKGROUND: It is not known whether the treatment costs of pancreatic surgery can be reduced by centralisation. The aim of this study was to analyse the impact of hospital volume on the short-term prognosis and costs in a nationwide study. METHODS: The National registry was searched for patients undergoing pancreatoduodenectomy (PD) in Finland between 2012 and 2014. Patient data was recorded up to ninety days postoperatively and Charlson comorbidity index (CCI) calculated. Complications were classified according to Clavien-Dindo. A CCI was calculated for each patient. The hospitals were categorized by yearly resection rate: high (≥20, HVC), medium (6-19, MVC) and low (≤5, LVC). Costs were calculated according to the 2012 billing list. RESULTS: The study population comprised 466 patients. Demographics were similar in the HVC, MVC and LVC groups. Mortality was lower in the HVCs than in MVCs and LVCs at 30 days (0.8% vs. 8.8-12.9%; p < 0.01) and at 90 days (1.9% vs. 10.5-16.1%; p < 0.01). Hospital volume and CCI were significant factors for mortality in multivariate analysis. Median costs among all patients were lower in the HVC group than in the MVC/LVC groups (p = 0.019), among Clavien-Dindo class III (0.020), among patients over 75 years (p < 0.001) and among patients who survived over five days (p = 0.015). CONCLUSIONS: Thirty- and 90-day mortality is 10 times lower when the patient is operated on in an HVC. The study shows that the median overall costs of surgical treatment are 82-88% of the median costs in lower volume centres.

Management of postoperative complications may favour the centralization of distal pancreatectomies. Nationwide data on pancreatic distal resections in Finland 2012-2014.

BACKGROUND: Centralization of pancreatic surgery has proceeded in the last few years in many countries. However, information on the effect of hospital volume specifically on distal pancreatic resections (DP) is lacking. AIM: To investigate the effect of hospital volume on postoperative complications in DP patients in Finland. METHODS: All DP performed in Finland during the period 2012-2014 were analyzed, information having been retrieved from the appropriate national registers. Hospital volumes, postoperative pancreatic fistulae (POPF) and overall complications were graded. High volume centre (HVC) was defined as performing > 10 DPs, median volume centre (MVC) 4-9 DPs and low volume centre (LVC) fewer than 4 DP annually. RESULTS: A total of 194 DPs were performed at 18 different hospitals. Of these 42% (81) were performed in HVCs (2 hospitals), 43% (84) in MVCs (6 hospitals) and the remaining 15% (29) in LVCs (10 hospitals). Patient demographics did not differ between the hospital volume groups. The overall rate of clinically relevant POPF, Clavien-Dindo grade 3-5 complications, and 90-day mortality showed no significant differences between the different hospital volumes. Grade C POPF was found more often in LVCs, being 1.2% in HVCs, 0% in MCVs and 6.9% in LVCs, p = 0.030. More reoperations were performed in LVCs (10.3%) than in HVCs (1.2%) or MVCs (1.2%); p = 0.025. CONCLUSIONS: Even though the rate of postoperative complications after DP is not affected by hospital volume, reoperations were performed ten times more often in the low-volume centres. Optimal management of postoperative complications may favour centralization not only of PD, but also of DP.

A serological marker of the N-terminal neoepitope generated during LOXL2 maturation is elevated in patients with cancer or idiopathic pulmonary fibrosis.

OBJECTIVES: Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation. DESIGN AND METHODS: An ELISA targeting the N-terminal site of the human LOXL2 was developed including technical optimization and validation steps. Serum LOXL2 was measured in patients with breast, colorectal, lung, ovarian, pancreatic and prostate cancer, melanoma, IPF and in healthy controls (n = 16). RESULTS: A technically robust and specific assay was developed. LOXL2 was detectable in serum from healthy controls and showed reactivity towards recombinant LOXL2. Compared to controls, LOXL2 levels were significantly (p < 0.001-0.05) elevated in serum from patients with breast, colerectal, lung, ovarian and pancreatic cancer (mean range: 49-84 ng/mL), but not in prostate cancer (mean: 36 ng/mL) and malignant melanoma patients (41 ng/mL). Serum LOXL2 was elevated in IPF patients compared to healthy controls (mean: 76.5 vs 46.8 ng/mL; p > 0.001). CONCLUSIONS: A specific ELISA towards the N-terminal neo-epitope site in LOXL2 was developed which detected significantly elevated serum levels from patients with above-mentioned cancer types or IPF compared to healthy controls.

The Accuracy of the Computed Tomography Diagnosis of Acute Appendicitis: Does the Experience of the Radiologist Matter?

BACKGROUND AND AIMS: To assess the accuracy of computed tomography in diagnosing acute appendicitis with a special reference to radiologist experience. MATERIAL AND METHODS: Data were collected prospectively in our randomized controlled trial comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (APPAC trial, NCT01022567). We evaluated 1065 patients who underwent computed tomography for suspected appendicitis. The on-call radiologist preoperatively analyzed these computed tomography images. In this study, the radiologists were divided into experienced (consultants) and inexperienced (residents) ones, and the comparison of interpretations was made between these two radiologist groups. RESULTS: Out of the 1065 patients, 714 had acute appendicitis and 351 had other or no diagnosis on computed tomography. There were 700 true-positive, 327 true-negative, 14 false-positive, and 24 false-negative cases. The sensitivity and the specificity of computed tomography were 96.7% (95% confidence interval, 95.1-97.8) and 95.9% (95% confidence interval, 93.2-97.5), respectively. The rate of false computed tomography diagnosis was 4.2% for experienced consultant radiologists and 2.2% for inexperienced resident radiologists (p = 0.071). Thus, the experience of the radiologist had no effect on the accuracy of computed tomography diagnosis. CONCLUSION: The accuracy of computed tomography in diagnosing acute appendicitis was high. The experience of the radiologist did not improve the diagnostic accuracy. The results emphasize the role of computed tomography as an accurate modality in daily routine diagnostics for acute appendicitis in all clinical emergency settings.

Effect of centralization on long-term survival after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Centralization of pancreatic surgery has resulted in improved short-term outcomes in a number of healthcare systems. The aim of this study was to see whether hospital volume influenced long-term prognosis, use of adjuvant therapy or histopathological evaluation of patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical resection of PDAC in Finland between 2002 and 2008 were identified from national registers. Demographic, histopathological, operative and oncological data were recorded, and the histopathological slides of patients who survived for more than 4 years were reviewed. Operative volume was defined according to the annual rate of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who had undergone resectional surgery for PDAC at 22 centres were included. Patient demographics and resection types did not differ between centres. Thirty- and 90-day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus 5·5 per cent (P = 0·001) and 2·5 versus 11·0 per cent (P = 0·003) respectively. Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage IIB: 65·7 versus 40·6 per cent respectively; P < 0·001), but with no greater use of adjuvant therapy. Significantly more patients survived for 2 years (43·3 versus 29·7 per cent; P = 0·034) and 3 years (25·4 versus 14·1 per cent; P = 0·045) after surgery in HVCs than in LVCs. More information was missing in the histopathological reports from LVCs and MVCs than in those from HVCs (P ≤ 0·002). CONCLUSION: Both short- and long-term survival was significantly better for patients operated on in HVCs. Histopathological analysis appears to be more comprehensive in HVCs.

Does Nissen Fundoplication Provide Lifelong Reflux Control? Symptomatic Outcome After 31-33 Years.

BACKGROUND: A substantial number of people are suffering from gastroesophageal reflux disease (GERD). The indication for surgical treatment is the failure of medical treatment in patients with objectively verified GERD. The use of PPIs has been noted to increase with the length of follow-up after fundoplication, raising questions concerning the durability of surgical results. The aim of the study was to investigate the results of open Nissen fundoplication (ONF) over a follow-up of more than 31 years. METHODS: ONF was performed for 38 consecutive patients. Questionnaires concerning long-term outcome were sent on December 14, 2015, to the 24 patients still living. Long-term symptom evaluation was carried out using the Gastrointestinal Symptom Rating Scale (GSRS), Visick grading, a Visual Analog Scale (VAS), the DeMeester-Johnson reflux scale, and the 15D tool. RESULTS: Seventeen (70.8%) of the 24 patients still living participated in the study. The typical symptoms of GERD had resolved significantly. Dysphagia was graded as none or minimal by 13 (81.3%) patients. The mean 15D score of the patient group was clinically and statistically the same (0.896 vs. 0.899) as that of the age- and sex-standardized general population (p = 0.912). Six (15.8%) patients had used antireflux medication after the operation and 4 of them (10.6%) continuously. CONCLUSIONS: Patients in the present study used PPIs less frequently than what has been reported in previous long-term follow-up studies. Our results indicate that successful surgery may provide lifelong relief of GERD symptoms and normalize the health-related quality of life in GERD patients.

Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders.

OBJECTIVES: Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer. DESIGN AND METHODS: Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls. RESULTS: The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls. CONCLUSIONS: MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.

A core needle biopsy provides more malignancy-specific results than fine-needle aspiration biopsy in thyroid nodules suspicious for malignancy.

BACKGROUND AND AIMS: The most commonly used diagnostic method for the preoperative diagnosis of thyroid nodules is ultrasound-guided fine-needle aspiration biopsy (FNA), which often yields non-diagnostic or non-definitive results and seldom produces definite malignant diagnoses. To improve upon the malignancy-specific sensitivity, we tested core needle biopsies (CNBs) of thyroid lesions taken from surgical specimens. MATERIAL AND METHODS: 52 consecutive patients with malignant or malignant-suspicious thyroid nodules were referred to Tampere University Hospital between May 2010 and December 2011. Preoperative FNAs were categorised as follicular neoplasm (48%), suspicion for malignancy (46%) or malignancy (6%). Intraoperative FNA and CNB samples were acquired from surgical specimens removed during surgery. The results of the needle biopsies were compared with the final pathological diagnosis. RESULTS: CNBs had a high definitive sensitivity for malignancy (61%, CI 41% to 78%) whereas the definitive sensitivity for malignancy of FNAs was significantly lower (22%, CI 10% to 42%). CNB was not beneficial in the diagnosis of follicular thyroid lesions. When all suspected follicular tumours were excluded, the definitive sensitivity of CNB rose to 70% (CI 48% to 86%). CONCLUSIONS: CNB may be beneficial for the diagnosis of papillary thyroid carcinoma and other non-follicular thyroid lesions. CNB may be considered as an additional diagnostic procedure in cases with FNA suspicious for malignancy.

Rising incidence of small size papillary thyroid cancers with no change in disease-specific survival in Finnish thyroid cancer patients.

BACKGROUND: The aim of this study was to investigate trends in the incidence, diagnostics, treatment and survival of thyroid cancer in Tampere University Hospital (TAUH) region in recent decades. MATERIAL AND METHODS: New thyroid cancer cases from 1981 to 2002 were ascertained from the Finnish Cancer Registry. Follow-up data was collected from medical records of TAUH. Differentiated thyroid cancer (DTC; consisting of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC)) patients' data was analyzed and divided into two equal time periods (1981-1991 and 1992-2002). RESULTS: The total amount of thyroid cancer cases was 553, of which 427 (77%) were papillary and 72 (13%) follicular. Thyroid cancer was four times more common in females than in males and the median age at the time of diagnosis was 52 years. The incidence of DTC was 4.5/100,000 in the earlier group and 6.0/100,000 in the later group (IRR 1.33, CI 1.11-1.60). The proportion of papillary thyroid cancer rose from 81% to 89% (p=0.02) in two study periods. Median tumour size became smaller, from 25 mm to 15 mm (p<0.001). Surgery became more radical as total thyroidectomies were performed almost exclusively on the later group (p<0.001). Median cumulative dose of radioiodine (I131) therapy was higher in the later group (p=0.04). There was no difference in number of cancer recurrences (p=0.54). The prognosis of DTC was good; 10-year disease-specific survival was 92% in the earlier group and 94% in the later group (p=0.43). CONCLUSIONS: The incidence of thyroid cancer has risen and proportion of papillary cancer has increased, however, median size of tumour has decreased. No difference was seen in either all-cause or disease-specific survival.

Distal pancreatectomy using a no-touch isolation technique.

BACKGROUND AND AIMS: Distal pancreatectomy is the only effective treatment for cancers of the pancreatic body and tail. The recurrence rate after DP has remained high. In an effort to over-come this problem, we developed a no-touch surgical technique for DP. This is a pilot study to see if distal pancreatectomy can be technically done using a no-touch surgical technique with-out deteriorating the post-operative prognosis. PATIENTS AND METHODS: From November 2000 through May 2011, 16 pancreatic ductal adeno-carcinoma patients have been operated on using a no-touch technique by a single operator. We described the surgical technique, and we reported our preliminary experience. During the procedure, the pancreatic body and tail is neither grasped nor squeezed by the surgeon. And all drainage vessels from the pancreatic body and tail are ligated and divided during the early phase of the operation. Furthermore, for improved dissection of the retroperitoneal tissue (rightward and posterior margins), we use a hanging and clamping maneuver and dissection behind Gerota's fascia. RESULTS: In the current series, the posterior and rightward resection margins were free in all patients, although seven were positive for anterior serosal invasion. The post-operative prognosis was not deteriorated with this technique. CONCLUSION: No-touch distal pancreatectomy technique may have some theoretical advantages, which merit future investigation in randomized controlled trials.

Protein kinase Cvarepsilon mediates Stat3Ser727 phosphorylation, Stat3-regulated gene expression, and cell invasion in various human cancer cell lines through integration with MAPK cascade (RAF-1, MEK1/2, and ERK1/2).

Protein kinase C epsilon (PKCvarepsilon), a novel calcium-independent PKC isoform, has been shown to be a transforming oncogene. PKCvarepsilon-mediated oncogenic activity is linked to its ability to promote cell survival. However, the mechanisms by which PKCvarepsilon signals cell survival remain elusive. We found that signal transducers and activators of transcription 3 (Stat3), which is constitutively activated in a wide variety of human cancers, is a protein partner of PKCvarepsilon. Stat3 has two conserved amino-acid (Tyr705 and Ser727) residues, which are phosphorylated during Stat3 activation. PKCvarepsilon interacts with Stat3alpha isoform, which has Ser727, and not with Stat3beta isoform, which lacks Ser727. PKCvarepsilon-Stat3 interaction and Stat3Ser727 phosphorylation was initially observed during induction of squamous cell carcinomas and in prostate cancer. Now we present that (1) PKCvarepsilon physically interacts with Stat3alpha isoform in various human cancer cells: skin melanomas (MeWo and WM266-4), gliomas (T98G and MO59K), bladder (RT-4 and UM-UC-3), colon (Caco-2), lung (H1650), pancreatic (PANC-1), and breast (MCF-7 and MDA:MB-231); (2) inhibition of PKCvarepsilon expression using specific siRNA inhibits Stat3Ser727 phosphorylation, Stat3-DNA binding, Stat3-regulated gene expression as well as cell invasion; and (3) PKCvarepsilon mediates Stat3Ser727 phosphorylation through integration with the MAPK cascade (RAF-1, MEK1/2, and ERK1/2). The results indicate that PKCvarepsilon-mediated Stat3Ser727 phosphorylation is essential for constitutive activation of Stat3 and cell invasion in various human cancers.

Helicobacter pylori in alcohol induced acute pancreatitis.

BACKGROUND AND AIMS: The objective of this study was to measure the association of Helicobacter pylori infection with alcoholic acute pancreatitis. MATERIAL AND METHODS: This study comprised of 50 patients with their first alcoholic pancreatitis and 50 alcoholic controls with no history of pancreatitis but similar alcohol use recruited from an alcohol rehabilitation center. Helicobacter infection was measured using Enzygnost EIA IgG-test. Complications and length of hospital stay were also recorded in patients with alcoholic pancreatitis. RESULTS: The seroprevalence of Helicobacter pylori was 10/50 (20%) in the pancreatitis group and 15/50 (30%) in the control group (p = NS). The median length of hospital stay of pancreatitis patients was 7 days, 11 days for those tested positive (range 6-25) and 6 days for those tested negative (range 3-47) for Helicobacter pylori, p = 0.013. As determined with the Atlanta criteria, seropositive patients tended to have more often severe pancreatitis, 4/10 (40%) vs. 6/40 (15%), OR 3.78 (95% CI 0.815-17.52), p = 0.097. CONCLUSIONS: This study suggests that Helicobacter pylori infection is not associated clinically significantly with the development of alcoholic pancreatitis. However, Helicobacter pylori infection may be associated with longer hospital stay due to more severe disease, which needs to be studied in a larger series of patients.

Late postoperative quality of life following pancreatic head resections.

BACKGROUND/AIMS: To evaluate health-related quality of life (HRQoL) in patients that have undergone pancreatic resection and compare the results with representative population samples in early and late stage evaluations. Also, this study aims to observe possible associations with postoperative complications. METHODOLOGY: Twenty-seven single-institute patients operated on during a 3-year period due to a benign or malignant process of the periampullary region. HRQoL was measured by the 15D instrument. Data were compared with those obtained from representative Finnish general population samples. RESULTS: Twenty-five patients were interviewed in the early stage (24 months postoperatively). Fifteen had a benign and 12 a malignant disease. No differences were found in the postoperative HRQoL when the nature of the disease or the postoperative complications were considered. When compared with the general population in the early stage, HRQoL was lower in the study group in whole, and also when sleep, elimination (bladder or bowel function) and sexual activity were considered separately. In the late stage evaluation (110 months postoperatively) the study group consisted of 15 surviving patients. There were no differences in comparison to the general population. Also when comparing the same patients in 2 evaluation points (24 and 110 months), we did not find any difference in any of the 15D parameters. CONCLUSIONS: Postoperative HRQoL deteriorated in comparison to general population in the early stage but there were no differences in the late stage. This study encourages us to continue the use of the 15D at least as a part of HRQoL evaluation, because it allows comparisons between different diseases and the general population.

Alcohol consumption in patients with acute or chronic pancreatitis.

Understanding of the relation between the alcoholic consumption and the development of pancreatitis should help in defining the alcoholic etiology of pancreatitis. Although the association between alcohol consumption and pancreatitis has been recognized for over 100 years, it remains still unclear why some alcoholics develop pancreatitis and some do not. Surprisingly little data are available about alcohol amounts, drinking patterns, type of alcohol consumed and other habits such as dietary habits or smoking in respect to pancreatitis preceding the attack of acute pancreatitis or the time of the diagnosis of chronic pancreatitis. This review summarizes the current knowledge. Epidemiological studies clearly show connection between the alcohol consumption in population and the development of acute and chronic pancreatitis. In the individual level the risk to develop either acute or chronic pancreatitis increases along with the alcohol consumption. Moreover, the risk for recurrent acute pancreatitis after the first acute pancreatitis episode seems also to be highly dependent on the level of alcohol consumption. Abstaining from alcohol may prohibit recurrent acute pancreatitis and reduce pain in chronic pancreatitis. Therefore, all the attempts to decrease alcohol consumption after acute pancreatitis and even after the diagnosis of chronic pancreatitis should be encouraged. Smoking seems to be a remarkable co-factor together with alcohol in the development of chronic pancreatitis, whereas no hard data are available for this association in acute pancreatitis. Setting the limits for accepting the alcohol as the etiology cannot currently be based on published data, but rather on the 'political' agreement.

Detection of postoperative pancreatitis after pancreatic surgery by urine trypsinogen strip test.

BACKGROUND: The urine trypsinogen strip test has been used successfully in the diagnosis of pancreatitis of various aetiologies, but has not been studied in postoperative pancreatitis. The aim of this study was to evaluate this test for the diagnosis of postoperative pancreatitis after pancreatic resection. METHODS: Fifty patients undergoing pancreatic resection were included. The urine trypsinogen strip test was done daily during the first postoperative week, blood was analysed before and 4, 6 and 10 days after surgery, and amylase activity in the drainage fluid was measured on days 4 and 6. Patients underwent computed tomography (CT) before operation and on days 2 and 6 afterwards. RESULTS: Thirteen patients (26 per cent) developed CT-detected pancreatitis after operation. In 12 of these patients pancreatitis was detected on the second postoperative day. The urine trypsinogen test was positive in all 13 patients with postoperative pancreatitis, and was already positive on the first day after surgery in 12. The sensitivity, specificity, and positive and negative predictive values of the trypsinogen strip test in detection of postoperative pancreatitis were 100, 92, 81 and 100 per cent respectively. In receiver-operator characteristic analysis the area under the curve (AUC) was higher for the urine trypsinogen strip test (AUC 0.959) than for a serum amylase level more than two (AUC 0.731) or three times (AUC 0.654) above the upper normal range in the diagnosis of postoperative pancreatitis. Patients whose recovery was complicated by pancreatic fistula, detected by drain output measurements on day 6, more often had a positive urine trypsinogen test than patients without a fistula (11 of 12 versus five of 38; P < 0.001). CONCLUSION: This study suggests that the urine trypsinogen strip test might be a valuable method for diagnosis of pancreatitis after pancreatic surgery.

The differentiation between pancreatic neoplastic cysts and pancreatic pseudocyst.

The number of small and often asymptomatic cystic lesions detected in pancreas has increased during the last decade. Historically the vast majority of the pancreatic cystic lesions were considered pseudocysts, but in recent series the incidence of various neoplastic cysts, such as intraductal papillary mucinous neoplasm, serous cystadenomas and cystic endocrine tumours, has increased. The possible malignant potential in these cystic neoplasms warrants careful diagnostic workup to choose the optimal treatment for each patient. Patient's age, symptoms and a possible history of acute or chronic pancreatitis with known aetiology together with high quality imaging studies are important in the differential diagnosis between pseudocysts and neoplastic cysts. Endoscopic ultrasound, cyst fluid analysis and positron emission tomography may be used in selected patients, but the accuracy of these methods needs further investigation.

Chest computed tomography in the staging of pancreatic and periampullary carcinoma.

BACKGROUND: Staging of the tumours in the pancreas and periampullary region usually consists of abdominal computed tomography (CT). Laparoscopy is also advocated. Little attention has been paid to extra-abdominal staging. In addition to peritoneal, lymphatic and hepatic metastases, lung metastases are frequently found. The chest CT scan has been demonstrated as better than the plain chest roentgenogram or conventional tomography in demonstrating lung tumours. This study was done to evaluate whether the chest CT scan gives information additional to the plain chest roentgenogram in the staging of pancreatic and periampullary tumours. METHODS: Fifty-three patients with a pancreatic or periampullary tumour underwent helical CT scan of the chest in addition to the abdominal CT scan. The CT scans and the chest roentgenograms were read separately without the result of the other being known; the results were compared with each other and with the clinical and operative findings. RESULTS: In the chest CT scan, 7 out of 53 (13%) patients had nodules in the lungs. The chest pathologies were not seen in the chest roentgenogram except for pneumonia in one patient and lung tumours in another (sensitivity of the chest roentgenogram 2/7 = 29%). Liver metastasis, local invasion of the tumour or poor general condition of the patient made lung biopsy or bronchoscopy unnecessary or impossible. CONCLUSION: Lung metastases seldom appear in patients with pancreatic or periampullary carcinoma without other contraindications for resection, which is why the chest CT scan cannot be recommended in the staging of these tumours for operation.